The research will increase our understanding of the mechanisms which are responsible for the trophic support of axons. Recent studies indicate that there are at least two subclasses of axonal microtubules. Proposed investigations focus on questions relating to subclasses of axonal microtubules. Are there regional differences in the polarity orientations of microtubules in other axons of other nervous systems, and are microtubule polarity orientations the same or different at synaptic and non-synaptic regions of an axon, or at nodal and inter-nodal regions of axonal membranes? How are longitudinal and polarity orientations of microtubules maintained? Are there regional differences in the predominant direction of particle transport in axons which have regionally specialized axoplasm or regionally different microtubule orientations? Two strategies are employed. One is to evaluate the regional distribution of microtubule polarities in selected vertebrate and invertebrate axons. The other is to determine whether the properties of vesicle and organelle transport are regionally different in identifiable axons which have unique distributions of axonal microtubules or other ultrastructural signs of a regionally specialized axoplasm. Axonal transport of trophic substances is essential for the normal functioning and survival of nerve cell axons. Microtubules are essential to the process of axonal transport, but their precise function is still unknown. Recent evidence outlined in this proposal indicates the possibility of a subclass of axonal microtubules which may function to direct trophic substances to their final targets. A congenital or disease related loss of just such a subclass of microtubules may account for certain neurological disorders. Because only a small fraction of axonal microtubules appear to belong to this subclass, previous studies may have failed to detect the loss.